文献：脂质聚乙烯亚胺结合物作为CpG寡脱氧核苷酸生物相容性载体对巨噬细胞的评价

链接：https://link.springer.com/article/10.1007/s12257-020-0366-1

作者：杨智媛，崔恩瑞，尤佳妍&穆慧静 

节选：

摘要

鉴于CpG寡脱氧核苷酸（CpG）具有强大的免疫刺激作用，开发CpG载体是实现高效癌症免疫*的先决条件。本研究将1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-[羟基琥珀酰亚胺（聚乙二醇）] (DSPE-PEG-NHS) 与聚乙烯亚胺 (PEI) 偶联，开发出一种PEI-PEG-DSPE偶联物，可作为生物相容性的高效CpG载体。我们开发了五种PEIPEG-DSPE偶联物，每种偶联物的PEI分子量不同，DSPEPEG的修饰程度也不同，均表现出显著较低的细胞毒性。具体而言，与通过天然PEI递送CpG相比，以摩尔比0.1递送PEI (25 kDa)-PEG-DSPE和DSPE-PEG-NHS/（PEI的胺基）可导致RAW264.7细胞对CpG的吸收更高，这可能是由于存在疏水性脂质部分。此外，PEI-PEG-DSPE/CpG复合物可诱导RAW264.7细胞显著分泌细胞因子（TNF-α），其作用与PEI/CpG复合物相当。因此，PEI-PEG-DSPE偶联物可作为生物相容性的高效载体，将免疫刺激剂CpG递送至巨噬细胞。

Abstract

Considering the potent immune stimulation by CpG oligodeoxynucleotides (CpGs), the development of CpG carriers is a prerequisite for efficient cancer immunotherapy. In this study, we conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxyl succinimidyl (polyethylene glycol)] (DSPE-PEG-NHS) with polyethylenimine (PEI) to develop a PEI-PEG-DSPE conjugate that can serve as a biocompatible and efficient CpG carrier. Five types of PEIPEG-DSPE conjugates were developed, each with different molecular weights of PEI and different degrees of DSPEPEG modification, and all exhibited significantly lower cytotoxicity. In particular, compared to CpG delivery via natural PEI, delivery with PEI (25 kDa)-PEG-DSPE and DSPE-PEG-NHS/(amine groups of PEI) at a molar ratio of 0.1 resulted in a higher uptake of CpGs into RAW264.7 cells, probably because of the presence of a hydrophobic lipid moiety. In addition, PEI-PEG-DSPE/CpG complexes triggered significant cytokine secretion (TNF-α) from RAW264.7 cells, comparable to that triggered by PEI/CpG complexes. Thus, PEI-PEG-DSPE conjugates could serve as biocompatible and efficient carriers of the immune stimulator CpG to the macrophages.

西安齐岳生物提供相关产品：

DSPE-PEG-FYPSYHSTPQRP（二硬脂酰基磷脂酰乙醇胺-聚乙二醇-*靶向蛋白)

DSPE-PEG-BSA

DSPE-PEG-RVG29

DSPE-PEG2000-GE11

DSPE-PEG4-acid

DPPE-PEG-cRGD

DSPE-PEG-P1(CSDSWHYWC)（二硬脂酰基磷脂酰乙醇胺-聚乙二醇-*靶向蛋白)

DSPE-PEG-NHS

DOPE-PEG-Biotin

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